ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3867C>T (p.Phe1289=) (rs138186428)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163550 SCV000214108 likely benign Hereditary cancer-predisposing syndrome 2014-07-24 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000198661 SCV000782004 likely benign Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514507 SCV000609638 likely benign not provided 2017-03-02 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000198661 SCV000692351 uncertain significance Neurofibromatosis, type 1 2016-06-03 no assertion criteria provided clinical testing
GeneDx RCV000514507 SCV000521062 likely benign not provided 2018-02-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000514507 SCV000696394 benign not provided 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The NF1 c.3867C>T (p.Phe1289Phe) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change located in the Rho GTPase activation protein domain (InterPro). One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect the binding sites for splicing enhancers. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 179/121342 control chromosomes (3 homozygotes) at a frequency of 0.0014752, which is approximately 7 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this variant is likely a benign polymorphism. This variant was found in Neurofibromatosis type 1 patients, including in one patient co-occurring with NF-1 c.1885G>A, p.G629R (not in our internal database, DM in HGMD) and was classified as a polymorphism (Mattocks_2004, Brinckmann_2007, Griffiths_2006). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Invitae RCV000198661 SCV000252684 benign Neurofibromatosis, type 1 2018-01-12 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000245250 SCV000711645 likely benign not specified 2017-03-07 criteria provided, single submitter clinical testing p.Phe1289Phe in exon 28 of NF1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.2% (156/66710) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs138186428).
PreventionGenetics RCV000245250 SCV000306261 benign not specified criteria provided, single submitter clinical testing

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